Autism Spectrum Disorders (ASDs) are complex lifelong neurodevelopmental and behavioral disorders manifesting in infancy or early childhood, characterized by impairments in social interaction and communication, and by repetitive, stereotyped behavior. Although the causes of ASD are unknown, the evidence suggests that the origins are likely the result of gene-environment interaction occurring in utero or very early in infancy. The prevalence of ASD appears to be on the rise in developed countries, and has become a serious public health concern. In most developing countries, however, the nature and prevalence of factors associated with ASDs are unknown. The long term goal of this planning project is to develop capacity for conducting large scale population-based Autism Spectrum Disorder (ASD) studies in Jamaica. The partners in this project are experienced researchers at The University of Texas Health Science Center at Houston (UTHSC-H) and Autism Speaks (AS), collaborating with a team of researchers in The University of West Indies (UWI) in Jamaica. The current ASD case-ascertainment in Jamaica is based on DSM-IV criteria and the Childhood Autism Rating Scale (CARS). We will provide training for ASD case-ascertainment based on Autism Diagnostic Interview-Revised (ADI-R) and Diagnostic Observation Schedule (ADOS) instruments and establish reliability. Using ADOS and ADI-R, we will re-evaluate about 250 CARS-identified ASD cases (age 2-8 years) from the Jamaica Autism Database, which is developed by our Jamaican collaborator, Dr Maureen Samms-Vaughan, at the UWI. The agreement between CARS and ADI-R will be determined. We will also conduct a pilot age and sex matched case-control study to investigate whether environmental exposures to mercury, lead, arsenic and cadmium play a role in autism. In addition, we will assess the role of select polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1), and their potential interactions with these heavy metals in relation to ASD. For both cases and controls we will administer a questionnaire to assess the demographic and socioeconomic position, occupation, smoking and drinking status of the parents. In addition, information about family history of developmental disorders, family size, birth order of the index child and whether the child is taking any medications will be collected. Furthermore, a dietary questionnaire aimed at capturing possible exposure to environmental contaminants such as lead, mercury, arsenic and cadmium will be administered. At the end of interview, 1-2 mLs of saliva and about 5 mLs of whole blood will be collected from the case and control children. The DNA isolation and analysis of polymorphisms will be conducted at the Center for Human Genetics at UTHSC-H School of Public Health. Blood samples will be analyzed for arsenic, cadmium, mercury and lead using a Perkin Elmer Elan DRC plus ICP Mass Spectrometer using the methodology described by the CDC protocols and adapted by the Michigan Department of Community Health Trace Metal Laboratory in Lansing, Michigan. PUBLIC HEALTH RELEVANCE: The prevalence of ASD appears to be on the rise in developed countries, and has become a serious public health concern. ASDs are complex lifelong neurodevelopmental and behavioral disorders and about 50% of ASD children suffer some degree of mental retardation and other developmental disorders. Reducing physical, psychological and economic burdens on the child, family and society may become possible through new knowledge of the potential environmental risk factors for ASD, and make decisions about avoiding exposure to environmental contaminants.